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Protocol Details

Use of Hepatitis B Immune Globulin (HBIg) to Restore Immune Control in Patients with Chronic Hepatitis B

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

18-DK-0116

Sponsoring Institute

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women and Fetuses;
Children

Special Instructions

Currently Not Provided

Keywords

HBsAg Loss;
Peginterferon;
Inactive Carrier

Recruitment Keyword(s)

None

Condition(s)

Chronic Hepatitis B

Investigational Drug(s)

Hepatitis B immune globulin

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: hepatitis B immune globulin (HBIg)
Drug: Pegylated interferon alfa (pegIFN)

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

Background:

Hepatitis B is a viral infection of the liver. When the immune system tries to clear hepatitis B, it damages the liver. Eventually, the immune system gets exhausted fighting the virus. Researchers want to see if giving large doses of an antibody (HBIg) with the drug peginterferon will boost the immune system in people with this disease.

Objectives:

To observe the effect of large doses of antibody against the hepatitis B surface antigen on the immune response to the virus. To see if removing hepatitis B surface antigen from the blood enhances the action of peginterferon.

Eligibility:

Adults ages 18 and older with hepatitis B

Design:

Participants will be screened twice with a medical history, physical exam, and blood and urine tests.

Participants will be randomly put in one of two groups. All participants will get peginterferon for 24 weeks. One group will first get HBIg for 12 weeks.

Participants in the combination group will have a 4-day clinic stay. They will have:

Repeats of screening tests

Eye exam

Liver ultrasound

The first dose of HBIg by IV over 2 hours

These participants will get HBIg at the clinic up to 8 times over 12 weeks then start the peginterferon.

All participants will get peginterferon for 24 weeks. They will get it by injection under the skin once a week. They may do this themselves. They will keep a drug diary. They will have 5 visits to assess response and monitoring for safety..

After stopping the study drug, participants will have 4 follow-up visits over 36 weeks. They will repeat screening tests and have 1 liver ultrasound.

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Eligibility

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

-Male or female >=18 years of age

-Known serum HBsAg positive with a level <1,500 IU/mL measured within 144 weeks of screening

-Hepatitis B e antigen negative at the time of screening

-HBV DNA levels <2000 IU/mL measured on two occasions at least 24 weeks and no more than 48 weeks apart, during screening

-ALT level <=1.5 ULN measured on two occasions at least 24 weeks and no more than 48 weeks apart, during screening

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

-Any treatment for HBV within the last 48 weeks

-Co-infection with HDV as defined by the presence of anti-HDV

-Co-infection with HCV as defined by the presence of anti-HCV with HCV RNA

-Co-infection with HIV as defined by the presence of anti-HIV

-Presence of anti-HBs

-Cirrhosis either diagnosed by a prior liver biopsy at any time or if not available by a transient elastography score >13 kPa.

-Decompensated liver disease as defined by serum bilirubin >2.5 mg/dL (with direct bilirubin > 0.5 mg/dL), prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3.5 g/dL, or a history of ascites, variceal bleeding or hepatic encephalopathy.

-Presence of other causes of liver disease, (i.e. hemochromatosis, Wilson disease, alcoholic liver disease, alpha-1-anti-trypsin deficiency).

-A history of organ transplantation, or in the absence of organ transplantation any medical condition requiring the chronic use of more than 5 mg of prednisone (or its equivalent) daily.

-Severe IgA deficiency

-Severe allergic reaction to any human immunoglobulin product

-Significant systemic illness other than liver diseases including congestive heart failure, renal failure, chronic pancreatitis, and diabetes mellitus with poor control, that in the opinion of the investigator may interfere with therapy.

-Pregnancy or for women of childbearing potential, inability or unwillingness to use an effective form of contraception during study participation.

-Lactating women.

-Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the liver that is suggestive of HCC, or an alpha-fetoprotein level of greater than 500 ng/mL

-eGFR < 50 ml/min, serum creatinine > 1.3 mg/dl

-History of hypersensitivity to pegylated interferon-alpha

-Platelet count <90 mm3/dL

-Hgb <12 g/dL for males and <11 g/dL for females

-Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, or personality disorder that, in the investigator s opinion, might interfere with participation in the study.

-History of malignancy or treatment for a malignancy within the past 3 years (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).

-History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.

-Presence of conditions that, in the opinion of the investigators, would not allow the patient to be followed in the current study.

-Inability of subject to understand and the unwillingness to sign a written informed consent document.


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Citations:

Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Batrla-Utermann R, Wang LY, You SL, Hsiao CK, Chen PJ, Chen CJ; R.E.V.E.A.L.-HBV Study Group. Spontaneous seroclearance of hepatitis B seromarkers and subsequent risk of hepatocellular carcinoma. Gut. 2014 Oct;63(10):1648-57. doi: 10.1136/gutjnl-2013-305785. Epub 2013 Nov 13.

Rehermann B. Pathogenesis of chronic viral hepatitis: differential roles of T cells and NK cells. Nat Med. 2013 Jul;19(7):859-68. doi: 10.1038/nm.3251.

Liang TJ, Block TM, McMahon BJ, Ghany MG, Urban S, Guo JT, Locarnini S, Zoulim F, Chang KM, Lok AS. Present and future therapies of hepatitis B: From discovery to cure. Hepatology. 2015 Dec;62(6):1893-908. doi: 10.1002/hep.28025. Epub 2015 Oct 27.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Marc G. Ghany, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)



Anna L. Rivero
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institutes of Health
Building 10
Room 4-5722
10 Center Drive
Bethesda, Maryland 20892
(301) 451-7007
anna.rivero@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03575208

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